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Pulling a ligase out of a “HAT” (555.13)
Author(s) -
Morgan Julie,
Greer Susanna
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.555.13
Subject(s) - ciita , pcaf , ubiquitin ligase , transactivation , ubiquitin , acetylation , biology , microbiology and biotechnology , histone , phosphorylation , cancer research , transcription factor , major histocompatibility complex , immune system , mhc class ii , genetics , gene
Major histocompatibility class II (MHC II) molecules present pathogenic and tumorigenic antigens to CD4 + T cells and play vital roles in regulating adaptive immune responses. MHC II is controlled at the level of transcription by the Class II Transactivator (CIITA) which is in turn regulated through a series of sequential posttranslational modification. Acetylation of CIITA by the histone acetyltransferase (HAT) pCAF, results in CIITA nuclear localization. Once nuclear, CIITA is ubiquitinated and binds the MHC II promoter. In addition to its HAT activity, pCAF was recently identified as an E3 ligase for the nuclear phospho protein Mdm2. We show here pCAF increases CIITA transactivation and ubiquitination; suggesting pCAF also drives CIITA ubiquitination. We have previously linked CIITA phosphorylation with subsequent mono‐ubiquitination and increased CIITA transactivation. We now further identify K63 linked ubiquitination of CIITA and provide novel links between acetylation, phosphorylation and ubiquitination of this critical inflammatory protein. Our data suggests particular posttranslational modifications of CIITA result in very different functional outcomes, and may enable the identification of biomarkers for immune diseases associated with dysregulated antigen presentation.